A multicenter, prospective, randomized, open-label, blinded endpoint trial of intravenous thrombolysis with tenecteplase for acute non-large vessel occlusion in extended time window (OPTION): Rationale and design

Background and Objectives: Recombinant human tenecteplase (TNK) tissue-type plasminogen activator (rhTNK-tPA, also named tenecteplase) is non-inferior to alteplase when given up to 4.5 hours after acute ischemic stroke (AIS) within 4.5 hours. Whether intravenous tenecteplase compared with supportive care improves the outcome of patients with AIS due to non-large vessel occlusion (non-LVO) between 4.5-24 hours is uncertain. The Tenecteplase for Acute Non-large vessel occlusion in the Extended Time Window (OPTION) trial aims to test the efficacy and safety of intravenous tenecteplase in patients presenting between 4.5-24 hours after symptom onset who have a non-LVO and evidence of salvageable tissue on perfusion imaging. Methods: OPTION is a multicenter, prospective, randomized, open-label, blinded endpoint (PROBE) study. Patients with AIS due to non-LVO and evidence of salvageable brain tissue within 4.5-24 hour time window meeting eligibility criteria will be allocated in a 1∶1 ratio to tenecteplase or standard medical treatment. A target mismatch profile is defined as ischemic core volume <50 mL, a mismatch ratio ≥1.2, and a mismatch volume ≥10 mL. A total of 568 patients will provide >80% power to detect a 12% absolute difference in the proportion of patients achieving an excellent functional outcome (modified Rankin scale [mRS] 0-1 at 90 days) at the two-sided 0.05 significance level. The primary efficacy outcome is excellent functional outcome (mRS 0-1) at 90 days. Secondary efficacy outcomes include disability level (ordinal distribution of mRS) at 90 days, functional independence (mRS 0-2) at 90 days, reperfusion at 24 hours, infarct volume at 24 hours, early clinical response at 24 hours, the National Institutes of Health Stroke Scale (NIHSS) change from baseline at 7 days/discharge, health status and quality of life at 90 days. Safety outcomes include symptomatic intracranial hemorrhage within 36 hours, systemic bleeding within 90 days, and mortality within 90 days. Discussion: The OPTION trial (NCT05752916) will provide evidence regarding the efficacy and safety of tenecteplase 4.5 to 24 hours in patients with AIS due to non-LVO.